Phenylketonuria, a hereditary disease resulting in high phenylalanine blood levels causes mental retardation in children. In phenylketonuric mothers it may cause cerebral injury to the genetically unaffected fetus. A phenylalanine degrading enzyme: phenylalanine ammonia lyase (PAL) was purified and immobolized to nylon tubes and to hollow fibers. We will continue to study reactors constructed from these fibers in vitro, for kinetic behavior and stability, and in vivo, in dogs and monkeys for physiologic and particularly hematologic effects as well as ability to lower high, induced phenylalanine levels. In vivo performance will be established upon repeated use in the same animals, to learn about possible immunologic side effects. Another phenylalanine degrading enzyme phenylalanine-hydroxylase (PH) will be purified and immobilized to the types of cartridges which were found to have optimal configurations. On the basis of the experiences with PAL, experiments yielding the most information will be repeated with PH-reactors. Phenylalanine will be double-labelled with tritium and deuterium to follow its metabolism in vivo upon breakdown with phenylalanine-ammonia-lyase and phenylalanine-hydroxylase carrying reactors. It is hoped that acceptable, therapeutically useful reactors can be developed in these studies for the prevention of phenylketonuria induced mental retardation.